Impact Of an Immune Modulator Mycobacterium-w On Adaptive Natural Killer Cells and Protection Against COVID-19

The kinetics of NKG2C ⁺ adaptive natural killer (ANK) cells and NKG2A ⁺ inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied for 6 months in a cohort of health-care workers following administration of heat killed Mycobacterium w (Mw group) in comparison to a control group. In both groups, COVID-19 correlated with a lower NKG2C ⁺ ANK cells at baseline. There was a significant upregulation of NKG2C expression and IFN-γ release in Mw group (p=0.0009), particularly in those with lower baseline NKG2C expression, along with downregulation of iNK cells (p<0.0001). This translated to a significant reduction in incidence and severity of COVID-19 in the Mw group (IRR-0.15, p=0.0004). RNA-seq analysis at 6 months showed an upregulation of ANK pathway genes and an enhanced ANK mediated ADCC signature. Thus, Mw was observed to have a salutary impact on the ANK cell profile and a long-term upregulation of ANK-ADCC pathways, which could have provided protection against COVID-19 in a non-immune high-risk population.